Bednarski, Patrick J. and Truembach, Barbara and Kratochwil, Nicole A. and Schönenberger, Helmut (1992) Diamine ligand release from the cisplatin analog [meso-1,2-bis(2,6-dichloro-4-hydroxyphenyl)ethylenediamine]dichloroplatinum(II) in cell culture medium. Journal of medicinal chemistry 35 (23), pp. 4479-4485.
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The stability of the five-membered chelate ring of the cisplatin analog [meso-1,2-bis(2,6-dichloro-4-hydroxyphenyl)ethylenediamine]dichloroplatinum(II) (I) was investigated under typical cell culture conditions (IMEM-Richter's medium with 10% fetal calf serum, 37 Deg). The platinum compd. was radiolabeled with tritium in the meta position of the arom. ring by an acid-catalyzed tritium-exchange reaction, and a reversed-phase HPLC assay with radiochem. detection was developed to monitor for the presence of the free diamine ligand in the cell culture medium. A gradual increase in radioactivity attributed to the free diamine was found in medium contg. the dichloroplatinum(II) complex (ca. 25% after 24 h), indicating that the diamine ligand was being released from the metal atom. When 1 mM glutathione (GSH) was included in the incubation medium, the amt. of free diamine nearly doubled after 24 h, while the amt. of radioactivity attributed to serum protein-platinum adducts decreased relative to incubations without GSH. On the other hand, the omission of serum form the incubations resulted in a dramatic decrease in the amt. of radioactivity eluting under the diamine peak, while the concns. of the 2 methionine-Pt adducts, which formed in a 1:1 ratio, rose. Through the use of liq. secondary ion mass spectroscopy, the 2 methionine-Pt adducts were identified as monomethionine metabolites of the title compd., whereby the 2 chloride ligands were replaced by the amino acid. These compds. are probably diastereomers since the sulfur of methionine can coordinate to platinum with equal probability either cis or trans to the R-configured benzylamine carbon. On the basis of the chem. shifts of the MeS groups in the 250-MHz 1H NMR, it is concluded that a S,N-five-membered chelate ring is present in these methionine-Pt adducts.
|Additional information (public):||CAN 117:225633 1-1 Pharmacology 105856-23-3 Role: ANST (Analytical study) (diamine ligand release from, in cell culture medium); 143707-47-5P Role: SPN (Synthetic preparation), PREP (Preparation) (prepn. and complexation of, with platinum); 143707-49-7P Role: SPN (Synthetic preparation), PREP (Preparation) (prepn. and formation in cell culture medium of); 143707-46-4P; 143707-48-6P Role: SPN (Synthetic preparation), PREP (Preparation) (prepn. of); 63-68-3 (Methionine) Role: RCT (Reactant), RACT (Reactant or reagent) (reaction of, with [bis(dichlorohydroxyphenyl)ethylenediamine]dichloroplatinum); 10025-99-7 (Dipotassium tetrachloroplatinate) Role: RCT (Reactant), RACT (Reactant or reagent) (reaction of, with bis(dichlorohydroxyphenyl)ethylenediamine); 111086-58-9 Role: PROC (Process) (release of, from platinum complex in cell culture medium)|
|Institutions:||Chemistry and Pharmacy > Institute of Pharmacy > Retired Professors > Prof. Schönenberger|
|Keywords:||Animal tissue culture (diamine ligand release from cisplatin analog in) diamine ligand release cisplatin analog cell|
|Subjects:||500 Science > 540 Chemistry & allied sciences|
|Refereed:||Yes, this version has been refereed|
|Created at the University of Regensburg:||Yes|
|Deposited On:||12 Nov 2010 07:00|
|Last Modified:||12 Nov 2010 07:00|